Résumé : Cet article analyse de façon détaillée les performances en matière d'emploi des immigrés de première et de deuxième génération en Belgique par rapport à celles des natifs. Les résultats ...montrent notamment que les immigrés de la première génération subissent une pénalité substantielle en matière d’emploi par rapport à leurs homologues natifs, mais aussi que leurs descendants continuent de rencontrer de graves difficultés pour accéder au marché du travail. Le rôle d’un grand nombre de variables modératrices, telles que le genre, l’éducation, le pays d’origine des immigrés et de leurs parents, la maîtrise de la langue nationale, la naturalisation, la durée de résidence et la raison de migration, est également discuté dans l’article.
Dans toute l’Europe, l’intégration des immigrés sur le marché du travail a tendance à être plus lente que celle des natifs. Cet article analyse empiriquement le rôle joué par les politiques ...d’intégration dans la réduction de cet écart dans les pays de l’Union européenne (UE). En nous appuyant sur l’indicateur de politique d’intégration pour migrants (MIPEX), nous constatons que les pays ayant des politiques plus développées en faveur de l’intégration des immigrés ne disposent pas nécessairement d’un taux d’emploi des personnes immigrées plus élevé. Cette constatation est due au fait que différents types de politiques ont des effets opposés : alors que les politiques favorisant le regroupement familial, luttant contre la discrimination et permettant la participation politique semblent augmenter l’intégration des personnes d’origine étrangère sur le marché du travail, une plus grande mobilité sur le marché du travail, ainsi qu’un accès plus large à la résidence permanente et à la nationalité sont négativement liés au taux d’emploi des immigrés. En outre, nos résultats confirment que l’intégration des immigrés sur le marché du travail varie en fonction de la composition des compétences de la population immigrée. Un plus haut niveau d’éducation favorise l’intégration. La composition de la population immigrée au sein d’un pays en termes de niveaux de qualifications, pourrait toutefois être également influencée par les politiques d’intégration dans les pays de destination potentiels, une hypothèse que nous testons également. Nous montrons que les politiques d’intégration agissent effectivement comme un facteur d’attraction. Cependant, il semble que les politiques d’intégration plus élaborées affectent principalement le nombre d’immigrés hautement qualifiés entrant sur le territoire, mais pas le nombre d’immigrés moyennement ou faiblement qualifiés. Des facteurs différents semblent donc être en jeu pour les personnes faiblement et moyennement qualifiées, mais une fois déplacées, nos résultats montrent que ce sont elles qui bénéficient le plus des politiques d’intégration.
Kappa class glutathione S-transferase (GST) cDNA sequences have been identified in rat, mouse, and human. In the present study, we determined the structure and chromosomal location of the human GST ...Kappa 1 (hGSTK1) gene, characterized the protein, and demonstrated its subcellular localization. The human gene spans ∼5 kb, has 8 exons, and maps onto chromosome 7q34. The 5′-flanking region lacks TATA or CCAAT boxes, but there is an initiator element overlapping the transcription start site. hGSTK1 amino acid sequence showed homology to bacterial 2-hydroxychromene-2-carboxylate isomerase, an enzyme involved in naphthalene degradation pathway. hGSTK1 mRNA was expressed in all of the organs examined. Subcellular fractionation of HepG2 cells showed that the protein was located in peroxisomes and mitochondria and was not detectable in cytoplasm. The peroxisomal localization was confirmed by transfection of HepG2 cells with a plasmid coding a green fluorescent protein fused inframe to the N terminus of hGSTK1. The C terminus of hGSTK1 was essential for localization of the protein to peroxisomes, and the C-terminal sequence Ala-Arg-Leu represents a peroxisome targeting signal. This is the first time that a human GST has been found in peroxisomes, suggesting a new function for this family of enzymes.
Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL), defined primarily by developmental delay/intellectual disability, speech delay, postnatal microcephaly, and ...dysmorphic features, is a syndrome resulting from heterozygous variants in the dosage‐sensitive bromodomain PHD finger chromatin remodeler transcription factor BPTF gene. To date, only 11 individuals with NEDDFL due to de novo BPTF variants have been described. To expand the NEDDFL phenotypic spectrum, we describe the clinical features in 25 novel individuals with 20 distinct, clinically relevant variants in BPTF, including four individuals with inherited changes in BPTF. In addition to the previously described features, individuals in this cohort exhibited mild brain abnormalities, seizures, scoliosis, and a variety of ophthalmologic complications. These results further support the broad and multi‐faceted complications due to haploinsufficiency of BPTF.
Molecular anomalies in
MED13L
, leading to haploinsufficiency, have been reported in patients with moderate to severe intellectual disability (ID) and distinct facial features, with or without ...congenital heart defects. Phenotype of the patients was referred to “
MED13L
haploinsufficiency syndrome.” Missense variants in
MED13L
were already previously described to cause the
MED13L
-related syndrome, but only in a limited number of patients. Here we report 36 patients with
MED13L
molecular anomaly, recruited through an international collaboration between centers of expertise for developmental anomalies. All patients presented with intellectual disability and severe language impairment. Hypotonia, ataxia, and recognizable facial gestalt were frequent findings, but not congenital heart defects. We identified seven de novo missense variations, in addition to protein-truncating variants and intragenic deletions. Missense variants clustered in two mutation hot-spots, i.e., exons 15–17 and 25–31. We found that patients carrying missense mutations had more frequently epilepsy and showed a more severe phenotype. This study ascertains missense variations in
MED13L
as a cause for
MED13L
-related intellectual disability and improves the clinical delineation of the condition.
Abstract
Buildings’ construction and operation are major contributors to global greenhouse gas (GHG) emissions, and the substantial reduction of GHG emissions across their full life cycle is required ...to enable meeting international climate targets. For effective climate change mitigation - as recent studies have shown - a special focus has to be put on lowering embodied GHG emissions, i.e., emissions related to construction production manufacturing and construction processes, maintenance and replacement as well as end-of-life processing. As the importance of reducing embodied GHG emissions rises, so does the need for understanding both the baseline and pathways for reduction across the full life cycle of buildings. In this paper, we offer insights into the data-driven analysis of embodied GHG emissions across the whole life cycle of buildings from recent studies. Our investigation builds on the data collection, processing and harmonisation of around 1.000 building LCA case studies. We offer an integrated perspective on GHG emissions across the life cycle of buildings, considering historical trends, current baselines and indicative reduction pathways for embodied GHG emissions in different countries across Europe. This serves to inform our current ‘decade of action’ and the transformation to a regenerative built environment by 2050.
Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently ...demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on electrophysiological properties of 59 of the variants in Xenopus oocytes using extended voltage and pH ranges. Detailed analyses revealed new pathophysiological mechanisms: 25% (15/59) of variants demonstrated LOF, characterized by a "shift" of the voltage-dependent activation to more positive voltages, and nine variants resulted in a toxic gain-of-function, associated with a disrupted gate allowing inward transport at negative voltages. Functional results were not always in line with in silico pathogenicity scores, highlighting the complexity of pathogenicity assessment for accurate genetic counselling. The complex neurocognitive and psychiatric manifestations of this condition, and hitherto under-recognized impacts on growth, gastrointestinal function, and motor control are discussed. Including published cases, we summarize features in 122 individuals from 67 families with CLCN4-related neurodevelopmental condition and suggest future research directions with the aim of improving the integrated care for individuals with this diagnosis.
AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs) mediate fast excitatory neurotransmission in the brain. AMPARs form by homo- or heteromeric assembly of subunits ...encoded by the GRIA1-GRIA4 genes, of which only GRIA3 is X-chromosomal. Increasing numbers of GRIA3 missense variants are reported in patients with neurodevelopmental disorders (NDD), but only a few have been examined functionally. Here, we evaluated the impact on AMPAR function of one frameshift and 43 rare missense GRIA3 variants identified in patients with NDD by electrophysiological assays. Thirty-one variants alter receptor function and show loss-of-function or gain-of-function properties, whereas 13 appeared neutral. We collected detailed clinical data from 25 patients (from 23 families) harbouring 17 of these variants. All patients had global developmental impairment, mostly moderate (9/25) or severe (12/25). Twelve patients had seizures, including focal motor (6/12), unknown onset motor (4/12), focal impaired awareness (1/12), (atypical) absence (2/12), myoclonic (5/12) and generalized tonic-clonic (1/12) or atonic (1/12) seizures. The epilepsy syndrome was classified as developmental and epileptic encephalopathy in eight patients, developmental encephalopathy without seizures in 13 patients, and intellectual disability with epilepsy in four patients. Limb muscular hypotonia was reported in 13/25, and hypertonia in 10/25. Movement disorders were reported in 14/25, with hyperekplexia or non-epileptic erratic myoclonus being the most prevalent feature (8/25). Correlating receptor functional phenotype with clinical features revealed clinical features for GRIA3-associated NDDs and distinct NDD phenotypes for loss-of-function and gain-of-function variants. Gain-of-function variants were associated with more severe outcomes: patients were younger at the time of seizure onset (median age: 1 month), hypertonic and more often had movement disorders, including hyperekplexia. Patients with loss-of-function variants were older at the time of seizure onset (median age: 16 months), hypotonic and had sleeping disturbances. Loss-of-function and gain-of-function variants were disease-causing in both sexes but affected males often carried de novo or hemizygous loss-of-function variants inherited from healthy mothers, whereas affected females had mostly de novo heterozygous gain-of-function variants.
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